Sickle Retinopathy Retinal Vasculitis and Radiation Retinopathy

Slide 1 · Sickle Retinopathy,

Retinal Vasculitis, and

Radiation Retinopathy

Retinal vascular injury, ischemia, neovascularization, and detachment

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Identify the shared ischemia-driven mechanism across the three retinal vascular disorders.

Relate sickle-cell vaso-occlusion to hemorrhage, characteristic fundus lesions, and sea-fan neovascularization.

Explain how vascular damage in vasculitis or after irradiation may lead to angiogenesis.

Trace retinal neovascularization to hemorrhage, membrane organization, traction, and detachment.

Slide 3 · Vascular injury is the organizing concept

Microvascular obstruction or injury

Retinal nonperfusion

Ischemic growth-factor response

Pathologic neovascularization

The initiating lesion differs among the three conditions.

Downstream consequences converge on hemorrhage, traction, and potential retinal detachment.

Slide 4 · The retina is a layered neurosensory tissue

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Preretinal blood

Intraretinal blood

Subretinal blood

Neurosensory retina lies internal to retinal pigment epithelium (RPE).

Hemorrhage position determines its structural context.

Vitreous lies immediately internal to the retinal surface.

Slide 5 · Retinal vascular injury can have two outputs

Blood-retinal barrier disturbance permits leakage, edema, hemorrhage, and exudation.

Vascular occlusion produces focal or regional retinal ischemia.

Ischemia induces proangiogenic signaling; Abnormal new vessels may form.

Neovascular membranes create mechanical as well as vascular complications.

Slide 6 · Occlusion and vessel-wall injury: Distinguish the starting event

Feature

Occlusion-dominant

Vessel injury–dominant

Initiating event

Impaired microvascular flow

Damage to existing retinal vessels

Exemplar in this lecture

Sickle retinopathy

Peripheral vasculitis; Irradiation

Shared consequence

Retinal ischemia / nonperfusion

Retinal ischemia / nonperfusion

Potential outcome

Growth-factor response and neovascularization

Growth-factor response and neovascularization

Slide 7 · Nonperfusion connects upstream and downstream pathology

Vascular obstruction

Poor tissue oxygen delivery

Retinal ischemia

Angiogenic signaling

The retinal periphery is particularly important for sickle retinopathy.

Ischemia is a mechanism; New-vessel formation is a response to that mechanism.

Slide 8 · Growth-factor signaling precedes proliferative lesions

Nonperfused retina

Increased VEGF and related factors

Abnormal retinal vessels

Proliferative retinopathy

VEGF is a shared mediator in ischemic retinal vascular disease.

VEGF and basic fibroblast growth factor are both implicated in sickle-retinal angiogenesis.

Slide 9 · Anatomic location separates stages of vascular retinopathy

Pattern

Predominant location

Underlying phenomenon

Nonproliferative

Within retina

Angiopathic and hemorrhagic lesions

Proliferative

Retinal surface or preretinal region

New abnormal vascular growth

Mechanical complication

Vitreoretinal interface

Organized membrane pulls on retina

Slide 10 · Internal limiting membrane marks the retinal surface

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Preretinal blood

Retina is bounded internally by the internal limiting membrane (ILM).

Preretinal hemorrhage is superficial to the neural retina.

New-vessel membranes can interact with posterior vitreous.

Slide 11 · The vitreoretinal interface converts growth into traction

Retinal neovascularization

Preretinal fibrovascular organization

Contraction and pull

Retinal displacement

Hemorrhage and fibroglial tissue organization change surface architecture.

A vessel lesion can evolve into a mechanical threat to retinal attachment.

Slide 12 · Retinal hemorrhages arise in different compartments

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Preretinal blood

Intraretinal blood

Subretinal blood

Preretinal blood is adjacent to the vitreoretinal interface.

Intraretinal blood occupies neural retinal layers.

Subretinal blood lies external to neurosensory retinal tissue.

Slide 13 · Location predicts the appearance of retinal hemorrhage

Location

Pathologic orientation

Clinical appearance

Nerve fiber layer

Parallel to retinal surface

Flame-shaped hemorrhage

Deeper retinal layers

Perpendicular to surface

Dot-like appearance

Preretinal / subhyaloid

Between retinal surface and posterior hyaloid

Superficial blood at vitreoretinal interface

Slide 14 · Hemorrhage and its organization can precede detachment

Preretinal hemorrhage

Organization of blood / tissue

Retinal traction

Retinal detachment

This sequence is specifically described in sickle retinopathy.

It highlights why even prior hemorrhage can have later structural consequences.

Slide 15 · Tractional and rhegmatogenous detachment differ

Characteristic

Tractional / nonrhegmatogenous

Rhegmatogenous

Primary mechanism

Pull from an organized surface membrane

Full-thickness retinal break allows vitreous fluid access

Retinal tear

Not required initially

Required

Important nuance

Severe traction can tear retina

May follow severe traction

Slide 16 · Three disorders, one ischemic retinal response

Disorder

Primary upstream insult

Convergent consequence

Sickle retinopathy

Low-O₂-induced red-cell sickling and occlusion

Peripheral ischemia; Angiogenesis

Retinal vasculitis

Injury to retinal vessels

Ischemia; Neovascularization

Radiation retinopathy

Retinal vascular injury following irradiation

Ischemia; Neovascularization

Slide 17 · Sickle hemoglobinopathy begins at the molecular level

β-globin point mutation

HbS present in erythrocytes

Deoxygenated HbS polymerizes

Red-cell distortion

The hemoglobin mutation is the initiating systemic mechanism.

The retinal lesion reflects its downstream microvascular consequences.

Slide 18 · Deoxygenation makes HbS erythrocytes less deformable

Normal-shaped erythrocytes

Distorted HbS-containing erythrocytes

HbS polymerization changes intracellular physical properties.

Progressive sickling distorts red cells.

Distorted, stiff cells participate in microvascular obstruction.

Schematic cellular forms — not a blood film

Slide 19 · Why microvascular transit matters

Slow capillary transit permits deoxygenated HbS to polymerize.

Sickled erythrocytes become mechanically less deformable.

Increased red-cell adhesion and local flow slowing can further promote obstruction.

Reduced perfusion creates conditions for additional regional hypoxia.

Slide 20 · Vaso-occlusion can reinforce itself

Reduced oxygen tension

Red-cell sickling

Microvascular obstruction

Further regional hypoxia

Repeated obstruction may sustain a cycle of impaired perfusion and deoxygenation.

The retinal periphery provides a particularly important low-oxygen microenvironment.

Slide 21 · Two genotypic settings for nonproliferative sickle retinopathy

Hemoglobin state

Status in this topic

Interpretation

HbSS

Nonproliferative retinal changes described

Sickle hemoglobinopathy with ocular risk

HbSC

Nonproliferative retinal changes described

Compound HbS/HbC sickling disorder

HbAS sickle trait

Ocular profile not established here

Requires separate evidence

Slide 22 · HbSC is a genuine sickling disorder

HbSC red cells contain substantial HbS, unlike normal HbAA erythrocytes.

HbC-associated cellular dehydration raises intracellular HbS concentration.

Deoxygenation can therefore trigger polymerization and microvascular manifestations.

Both HbSC and HbSS occur among genotypes associated with nonproliferative sickle retinopathy.

Slide 23 · Low oxygen tension emphasizes the retinal periphery

The peripheral retinal microcirculation is the emphasized site of sickling.

Regional vaso-occlusion generates nonperfused retina.

The ischemic territory may subsequently drive angiogenic signaling.

Schematic retinal field — not an ophthalmoscopic image

Slide 24 · Nonproliferative sickle retinopathy: Core concept

The nonproliferative stage is characterized by intraretinal angiopathic changes.

Occlusions contribute to preretinal, intraretinal, and subretinal hemorrhages.

Resolved hemorrhages generate recognizable ophthalmoscopic signs.

Proliferation is a separate stage characterized by neovascularization.

Slide 25 · Sickle-cell hemorrhages span retinal compartments

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Preretinal blood

Intraretinal blood

Subretinal blood

Preretinal, intraretinal, and subretinal hemorrhage are all described.

Their different positions imply different surface and tissue effects.

Organization of preretinal blood is particularly relevant to traction.

Slide 26 · Preretinal hemorrhage can become a traction source

Blood accumulates at or near the retinal surface.

An organized preretinal hemorrhage can produce fibrous tissue.

Contraction may pull on the underlying retina.

The resulting traction can contribute to retinal detachment.

Slide 27 · Intraretinal hemorrhage indicates vascular injury inside retina

Occluded retinal microvessels can be associated with intraretinal bleeding.

Hemorrhage occurs within the layered neurosensory tissue.

Its subsequent resolution may leave clinically visible abnormalities.

Intraretinal disease does not itself establish proliferative retinopathy.

Slide 28 · Subretinal hemorrhage occupies the RPE–retina interface

The hemorrhage lies external to the neurosensory retina.

This compartment may be involved in nonproliferative sickle retinopathy.

It is anatomically distinct from preretinal and intraretinal bleeding.

Site must not be confused with the presence of a full-thickness retinal tear.

Slide 29 · Salmon patches: A residual hemorrhagic sign

An ophthalmoscopically recognized finding in sickle retinopathy.

Appears among changes associated with resolution of retinal hemorrhage.

This finding alone does not establish a sea-fan proliferative lesion.

Schematic retinal field — not an ophthalmoscopic image

Slide 30 · Iridescent spots: A recognizable posthemorrhagic change

Iridescent spots may remain following resolution of hemorrhage.

They belong to the described nonproliferative lesion spectrum.

An illustrated mark is not a substitute for an authentic clinical photograph.

Schematic retinal field — not an ophthalmoscopic image

Slide 31 · Black sunburst lesions: Peripheral pigmented-appearing marks

Named ophthalmoscopic finding in sickle retinopathy.

These lesions are grouped with changes following hemorrhage resolution.

Their appearance should not be mistaken for the sea-fan neovascular lesion.

Schematic retinal field — not an ophthalmoscopic image

Slide 32 · Three classic fundus descriptors do not mean the same thing

Finding

Pathologic association

Teaching interpretation

Salmon patches

Hemorrhage-resolution changes

Recognize hemorrhagic history

Iridescent spots

Hemorrhage-resolution changes

Recognize nonproliferative aftermath

Black sunburst lesions

Hemorrhage-resolution changes

Do not confuse with sea-fan growth

Sea fans

Florid peripheral neovascularization

Identify proliferative response

Slide 33 · Nonproliferative lesions reflect vascular occlusion

Peripheral sickling

Microvascular occlusion

Hemorrhage in retinal compartments

Visible residual lesions

Salmon patches, iridescent spots, and black sunbursts are named results of hemorrhage resolution.

They illustrate the morphological footprint of earlier microvascular disease.

Slide 34 · Ischemia explains the transition to neovascular disease

Peripheral nonperfusion

Local retinal hypoxia

Increased angiogenic signals

Peripheral new vessels

An ischemic retinal microenvironment can drive proliferative disease.

The same general sequence appears in several retinal vascular conditions.

Slide 35 · Two growth factors named in sickle retinopathy

Vascular endothelial growth factor (VEGF) is upregulated with retinal ischemia.

Basic fibroblast growth factor (bFGF) is also implicated in the angiogenic response.

These signals are linked to retinal angiogenesis downstream of vascular occlusion.

Their mention does not establish a treatment response or biomarker cut-off.

Slide 36 · Proliferative sickle retinopathy is defined by new vessels

The clinically important transition is the appearance of retinal neovascularization.

The new vessels are especially prominent in the retinal periphery.

Florid peripheral retinal neovascularization forms characteristic “sea fans.”

The consequence of proliferation is not limited to bleeding: Organized tissue may exert traction.

Slide 37 · Sea fans: The characteristic proliferative lesion

Peripheral florid retinal neovascularization.

Linked to occlusion, ischemia, and local angiogenic growth factors.

Represents proliferative, not merely hemorrhagic, retinal disease.

Schematic retinal field — not an ophthalmoscopic image

Slide 38 · Location of sea fans matters to disease mechanism

A peripheral ischemic field is the stated upstream context.

The neovascular lesion occupies the peripheral retinal region.

Bleeding and traction may arise from pathological vessels or their organization.

Schematic retinal field — not an ophthalmoscopic image

Slide 39 · New vessels create hemorrhagic consequences

Ischemia-induced new vessels

Pathologic preretinal vascular tissue

Hemorrhagic complication

Blood near retina or vitreous

Pathologic retinal angiogenesis may be followed by bleeding.

Retinal neovascularization can bleed into the avascular vitreous.

Slide 40 · Organization turns hemorrhagic lesions into traction

Preretinal hemorrhage

Organization and fibrovascular tissue

Retinal surface traction

Potential detachment

Mechanical effects can continue after an initial bleeding event.

Traction couples vascular pathology to anatomy of vitreous and retinal attachment.

Slide 41 · Traction can separate neurosensory retina from RPE

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Mechanical pull on retina

Neovascular or hemorrhagic material can organize on the retinal surface.

Contraction transmits a pulling force onto the retina.

Separation from RPE defines retinal detachment.

Slide 42 · Sickle nonproliferative vs proliferative disease

Feature

Nonproliferative

Proliferative

Main process

Intraretinal angiopathy / hemorrhage

New retinal vessels

Named signs

Salmon patches, iridescent spots, black sunbursts

Sea fans

Ischemic mechanism

Occlusion already present

Hypoxic growth-factor upregulation

Major structural concern

Organization of preretinal blood

Hemorrhage and fibrovascular traction

Slide 43 · Application: Hemorrhage versus proliferation

Teaching vignette — hypothetical

A teaching fundus description in a person with HbSS includes multiple residual hemorrhagic lesions but no stated peripheral sea-fan neovascularization.

Interpretation prompts

Which disease phase is described?

Which findings would establish a proliferative lesion?

What additional structural complication can follow preretinal hemorrhage?

Slide 44 · Interpreting the sickle case

Residual hemorrhagic lesions are compatible with nonproliferative morphology.

Peripheral sea-fan neovascularization would indicate proliferative disease.

The absence of an explicitly described sea fan should not be read as proof of absent angiogenesis.

Organized preretinal hemorrhage can exert traction even in the discussed nonproliferative pathway.

Slide 45 · Sickle retinopathy: Two related paths from occlusion

Low-O₂ sickling

Vascular occlusion

Hemorrhage or retinal ischemia

Residual lesions or sea fans

Both outcomes emerge from occlusive microvascular disease.

Retinal hemorrhages and neovascularization are linked but are not synonymous.

Slide 46 · Retinal vasculitis begins with injury to retinal vessels

Peripheral retinal vasculitis can be associated with retinal neovascularization.

Vessel-wall damage, not HbS polymerization, is the initiating disease process.

Injured retinal vessels can create nonperfused ischemic zones.

The morphology does not, by itself, identify a specific systemic vasculitis.

Slide 47 · Peripheral vasculitis can leave ischemic retinal sectors

Vessel injury can impair perfusion in an affected retinal region.

Ischemic zones provide an angiogenic stimulus.

A schematic ischemic sector does not establish a particular angiographic pattern.

Schematic retinal field — not an ophthalmoscopic image

Slide 48 · Vasculitis: Vascular damage to abnormal angiogenesis

Peripheral retinal vasculitis

Retinal vessel damage

Ischemic retinal region

Retinal neovascularization

The causal sequence is explicitly grouped with sickle and radiation retinopathy.

No particular inflammatory cause is assumed here.

Slide 49 · Complications of vasculitis-associated proliferation

Neovascularization

Hemorrhage

Organization / traction

Retinal detachment

The same mechanical end-stage may follow distinct initiating conditions.

Recognizing vessel damage is more informative than labelling all cases as sickle disease.

Slide 50 · Retinal ischemia does not identify the vasculitis cause

Retinal vasculitis is one route to retinal vessel damage and ischemia.

The downstream ischemic pattern alone does not identify an etiology.

Specific etiologic diagnosis requires additional clinical and laboratory evidence.

Regardless of cause, ischemia-driven neovascularization may lead to traction.

Slide 51 · Radiation retinopathy: The initiating clinical setting

Irradiation for an intraocular tumor provides the initiating clinical context.

Retinal vascular damage is the highlighted pathological link.

Resulting nonperfusion may promote ischemia-driven angiogenesis.

Retinal morphology alone does not establish an irradiation dose or exposure timeline.

Slide 52 · Radiation injury converges on retinal nonperfusion

Irradiation of intraocular tumor

Damage to retinal vessels

Zones of ischemia

Growth-factor-driven angiogenesis

Exposure and endothelial/vascular injury are conceptually upstream.

The central mechanistic link is vascular nonperfusion followed by angiogenesis.

Slide 53 · Radiation-associated retinal injury may create ischemic zones

After irradiation, vessel damage can disturb retinal perfusion.

Regions of ischemia provide the substrate for new-vessel signaling.

This is a mechanistic schematic, not a post-radiotherapy clinical photograph.

Schematic retinal field — not an ophthalmoscopic image

Slide 54 · Radiation retinopathy: Proliferative consequences

Retinal vessel damage

Ischemic angiogenic response

New vessels and hemorrhage

Traction ± detachment

The result parallels the downstream events in vasculitis.

No timing or incidence claim is made beyond the supplied textbook passage.

Slide 55 · Why radiation retinopathy is grouped with vasculitis

Neither requires sickle hemoglobin polymerization as the initiating insult.

Both can injure retinal vessels and leave poorly perfused retinal tissue.

Neovascular growth is a secondary reaction to this ischemia.

Bleeding and membrane traction can threaten retinal attachment.

Slide 56 · Vasculitis and irradiation: Different causes, same pathway

Feature

Peripheral retinal vasculitis

Radiation retinopathy

Initiating setting

Inflammatory vessel injury

Irradiation for intraocular tumor

Primary retinal problem

Vessel damage / nonperfusion

Vessel damage / nonperfusion

Ischemic response

Retinal angiogenesis

Retinal angiogenesis

Possible complications

Hemorrhage, traction, detachment

Hemorrhage, traction, detachment

Slide 57 · All three converge on one pathobiologic sequence

Impaired microvascular flow

Nonperfused retina

Ischemia-induced angiogenesis

Hemorrhage and traction

Sickle disease begins in red cells; Vasculitis and radiation begin in damaged vessels.

This shared end pathway is why they are taught together.

Slide 58 · Identify the initiating lesion before assigning a diagnosis

Disorder

Supported upstream mechanism

What is not justified from morphology alone

Sickle retinopathy

HbS-related peripheral microvascular occlusion

Do not infer hemoglobin genotype from a sea fan alone

Retinal vasculitis

Injury to vessels in peripheral retinal vasculitis

Do not infer a named systemic disorder

Radiation retinopathy

Irradiation-associated vessel damage

Do not infer dose or timing

Slide 59 · Shared VEGF biology links neighboring retinal disorders

Diabetic retinopathy also features ischemia-associated VEGF upregulation.

Retinopathy of prematurity also involves proliferation following retinal ischemia.

The three conditions in this lecture share the broad ischemia-to-angiogenesis logic.

Identical signaling logic does not imply identical causes, classifications, or treatments.

Slide 60 · Why tractional retinal detachment is a distinct complication

Vitreous

ILM + inner retina

Middle retinal layers

Outer retina

RPE

Mechanical pull on retina

Vitreoretinal membranes exert a mechanical pull on neural retina.

Detached neurosensory retina separates from underlying RPE.

Severe traction can ultimately cause a tear and superimposed rhegmatogenous detachment.

Slide 61 · Three brief scenarios: Identify the mechanism

Teaching vignette — hypothetical

A: HbSC disease with peripheral hemorrhagic lesions.

B: Peripheral retinal vasculitis and zones of nonperfusion.

C: Intraocular irradiation followed by retinal neovascularization.

Interpretation prompts

Which upstream lesion fits each?

What downstream pathway do all three share?

Which findings represent proliferative rather than hemorrhagic disease?

Slide 62 · Answers: Recognize mechanism before complication

Scenario

Upstream abnormality

Downstream concern

A — HbSC

Peripheral red-cell sickling and occlusion

Hemorrhage ± sea-fan neovascularization

B — vasculitis

Retinal vessel damage

Ischemia, neovascularization and traction

C — irradiation

Radiation-associated vessel injury

Ischemia, neovascularization and traction

Slide 63 · Three routes to retinal structural damage

Starting point

Intermediate process

Possible endpoint

Sickle preretinal hemorrhage

Organization of blood

Retinal traction / detachment

Sickle sea-fan neovascularization

Preretinal abnormal vascular tissue

Hemorrhage / traction

Vasculitis or irradiation

Vascular damage → ischemic neovascularization

Hemorrhage / traction / detachment

Slide 64 · Clinicopathologic synthesis

Primary lesion: Intraretinal vascular occlusion or damage.

Ischemic retina upregulates proangiogenic signals; VEGF is particularly emphasized.

Proliferative new vessels are distinct from residual nonproliferative hemorrhagic lesions.

Hemorrhage and organized tissue produce traction, potentially separating retina from RPE.

Slide 65 · Clinical distinctions worth retaining

Salmon patches, iridescent spots, and black sunbursts follow retinal hemorrhage; sea fans indicate neovascularization.

Sickle retinopathy begins with HbS-related microvascular obstruction, especially in the retinal periphery.

Retinal vasculitis and irradiation damage vessels, but both can converge on ischemic angiogenesis.

Hemorrhage, membrane organization, and traction explain how a vascular disorder may culminate in retinal detachment.